263MO - Variant allele frequency and copy number gain in EGFR mutated lung cancer: A menace or a boon?

Background

EGFR mutant NSCLC comprises the largest molecular subgroup in NSCLC, with remarkable responses to targeted therapy. However a third of the patients do not respond, and among the responders there exists a heterogeneity in response. A better understanding is still needed of the various attributes of the EGFR mutation itself, apart from the widely studied primary resistance mechanisms. Variant Allele frequency (VAF) which is influenced by tumor proportion, and copy number alteration of the gene is an important attribute and a possible predictor of outcome and response.

Methods

126 patients of EGFR mutated NSCLC were subjected to panel based NGS testing. VAF and EGFR copy numbers were recorded and correlated with clinicopathological features and survival outcomes. A VAF of >50% was considered as high VAF, after evaluation by receiver operator curve analysis.

Results

Of 126 EGFR-mutant patients, 67 (53.2%) had exon 19 deletion, while 41 (32.5%) and 18 (14.%) patients had uncommon mutations. EGFR-VAF was significantly higher in patients with exon 19 mutations than in those with exon 21(P<0.003). Exon 19 patients showed a significantly improved PFS (P=0.04) and OS (P=0.07) compared to exon 21 patients. Irrespective of mutation type, a statistically significant association was found between VAF and PFS (P=0.001). High (≥50%) EGFR-VAF was independently associated with a longer PFS [vs. low (<50%) ; median PFS were 12.4 months vs. 9.2 months respectively; P<0.05]. Copy number gain in EGFR more than 5.5 was associated with better PFS of 11.2 months when compared to those with normal copy number. However, copy number gain co-occurring with exon 20 insertion mutation was associated with a shorter PFS (7.2 months vs 12.8 months; p<0.04) when compared to other EGFR subgroups with high copy numbers.

Conclusions

VAF is an important attribute in a panel based NGS report, impacting treatment outcomes and patient survival. This is the first of its kind study from India highlighting the same, and the data on the same from more real world studies are needed for the institution of recommendations for routine reporting of VAF in all such cases.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Ullas Batra.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.